The development of malignant tumor may be related to the failure of cells to die when they should. Apoptosis is a natural form of cell death that can be induced in leukemic cells by dexamethasone, a synthetic glucocorticoid steroid. Once initiated the cell follows a programmed course actively participating in the process leading to its own death. The process by which cells undergo apoptotic cell death is very complicated and currently not understood. The goal of this project is to characterize aspects of glucocorticoid induced apoptosis in leukemic cells in order to gain a better understanding of the mechanisms of apoptosis and glucocorticoid resistance. Since intermediates of phospholipid pathways have been implicated in the regulation of cellular activities, the possibility that these intermediates are involved in the complex signalling crucial to the control of apoptosis will be investigated. Multinuclear NMR techniques together with isotopically labelled metabolites will be used to characterize the phospholipid metabolism and alterations in the composition of cell membrane during apoptosis. The role of macromolecular (proteins, DNA, RNA) synthesis and degradation during apoptosis will also be investigated. One dexamethasone (dex) sensitive and three different dexamethasone resistant cell lines will be used in order to evaluate the receptor mediated contributions. The results of these studies will be compared and contrasted among the four cell lines for new insight into the mechanisms of dex-induced apoptosis and dex-resistance. Potentially, a good understanding of the mechanisms involved in apoptosis and glucocorticoid resistance could be very useful in designing new and more effective therapies for cancer.